Interstitial Cystitis (IC) is a chronic disease of the urinary tract which affects at least 10 out of 100,000 people, of whom 90% are women; Some estimates are much higher. It is a disease characterized by urinary frequency and urgency nocturia and suprapubic pain. Diagnosis depends on the presence of the aforementioned symptoms and the absence of any other disease which might produce those symptoms (e.g., cancer or infection). Treatment is non-specific and is not very successful; in extreme cases, major surgery is indicated. Many patients also suffer psychological discomfort due to the symptoms of the disease, their refractory response to treatment, and the inability of physicians to clearly define the disease. Although histology of the bladder in IC reveals some inflammatory infiltrates, there has been no systematic investigation into inflammatory mediators and IC. In the present experiments, we will be investigating the role of inflammatory mediators in the onset and maintenance of IC. Findings in IC patients will be compared with normal controls, patients with stress incontinence and those with bacterial cystitis. Urine, bladder wash fluid and bladder biopsy specimens will be examined for the presence of inflammatory cells. Urinary levels of inflammatory mediators, including prostaglandins, leukotriences, cachectin/tumor necrosis factor, interleukin-1, interleukin-6 and platelet-activating factor will be measured. In addition, bladder specimens obtained from biopsies (done in the past or in newly diagnosed patients) will be examined by histochemical methods for the presence of inflammatory mediators or enzymes involved in their synthesis. Messenger RNA of inflammatory mediators or enzymes will also be examined in cells in the bladder wash fluid or in biopsy specimens. Since, there is precedent in the literature to suggest that substances in the urine may initiate or exacerbate bioactivity or synthesis. It is hoped that the results of these experiments will provide insight into the contribution of inflammatory mediators to this disease, which will lead to a better understanding of its etiology. As the etiology of IC is better understood, both diagnosis and therapy of this chronic, sometimes disabling, disease can be improved.